分子对接研究了解生姜化合物(6-姜辣素和6-姜酚)在抗血管生成和抗淋巴管生成机制中的潜在作用

S. Nanchari, Shyam Perugu, V. Venkatesan
{"title":"分子对接研究了解生姜化合物(6-姜辣素和6-姜酚)在抗血管生成和抗淋巴管生成机制中的潜在作用","authors":"S. Nanchari, Shyam Perugu, V. Venkatesan","doi":"10.5539/ijc.v12n1p61","DOIUrl":null,"url":null,"abstract":"Background- 6-Gingerol and 6-Shogaol are novel biologically active phenol compounds isolated from rhizomes of Ginger (Zingiber officinale Roscoe), which has a potential role as anti-inflammatory, anti-oxidant and apoptotic. Till date there are no scientific reports on the functional properties of Ginger against the molecular mechanisms of angiogenesis, lymphangiogenesis, and metastasis. Hence, in the present study we have explored the feasibility of active ginger compounds (6-Gingerol and 6-Shogaol) to validate their molecular mechanisms on angiogenesis and lymphangiogenesis in breast cancer progression through in silico approach. Methodology- Studies have been targeted to find the interactions between selected protein receptors, which play a pivotal role in angiogenesis and lymphangiogenesis and ligands of Ginger compounds (6-Gingerol and 6-Shogaol) by using Accelrys discovery studio 2.5, followed by analysis of data. Results- Based on the in silico approaches, we found the best interactions between ginger compounds (6-Gingerol and 6-Shogaol) and targeted protein molecules as shown less than 3.10 A0H-bond distance to indicate higher binding affinity and stronger interactions and high docking scores. We demonstrate docking interactions of 6-Gingerol with the proteins involved in angiogenesis like VEGF-A (3QTK), VEGFR-1 (5ABD), VEGFR-2/VEGF-E COMPLEX (3V6B, Angiopoietin-2 (4JZC), PDGF-B (4QCI), KDR (5EW3) and with the proteins involved in lymphangiogenesis such as VEGF-C(2XIX), VEGF-C in complex with domains of 2 and 3 of VEGFR2 (2X1W), NRP2(4QDS) and Neuropilin-1/VEGF-A complex (4DEQ). Similarly, our data shows that 6-Shogaol also interacts with angiogenic specific proteins, like [VEGF-A (3QTK), VEGFR-1 (5ABD), VEGFR-2/VEGF-E COMPLEX (3V6B), Angiopoietin-2 (4JZC), PDGF-B (4QCI), KDR (5EW3)] and lymphangiogenesis [VEGF-C(2XIX), VEGF-C in complex with domains of 2 and 3 of VEGFR2 (2X1W), NRP2(4QDS) and Neuropilin-1/VEGF-A complex (4DEQ)]. Discussion- In silico approaches suggest a stronger binding affinity between the ginger compounds (6-Gingerol and 6-Shogaol) and selected proteins critical in angiogenesis and lymphangiogenesis. The present study underlines the feasibility of neutraceuticals to target the pathways participating in breast cancer progression through neovascularization. Our results also advocate 6-Gingerol to be more potent inhibitor of lymphangiogenesis assessed by its binding efficacy with VEGF-C and NRP2 (4QDS) as compared against 6-Shogaol.","PeriodicalId":13866,"journal":{"name":"International Journal of Chemistry","volume":"242 1","pages":"61-68"},"PeriodicalIF":0.0000,"publicationDate":"2019-12-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"1","resultStr":"{\"title\":\"Molecular Docking Studies to Understand the Potential Role of Ginger Compounds (6-Gingerol and 6-Shogaol) on Anti-Angiogenic and Anti-Lymphangiogenic Mechanisms\",\"authors\":\"S. Nanchari, Shyam Perugu, V. Venkatesan\",\"doi\":\"10.5539/ijc.v12n1p61\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"Background- 6-Gingerol and 6-Shogaol are novel biologically active phenol compounds isolated from rhizomes of Ginger (Zingiber officinale Roscoe), which has a potential role as anti-inflammatory, anti-oxidant and apoptotic. Till date there are no scientific reports on the functional properties of Ginger against the molecular mechanisms of angiogenesis, lymphangiogenesis, and metastasis. Hence, in the present study we have explored the feasibility of active ginger compounds (6-Gingerol and 6-Shogaol) to validate their molecular mechanisms on angiogenesis and lymphangiogenesis in breast cancer progression through in silico approach. Methodology- Studies have been targeted to find the interactions between selected protein receptors, which play a pivotal role in angiogenesis and lymphangiogenesis and ligands of Ginger compounds (6-Gingerol and 6-Shogaol) by using Accelrys discovery studio 2.5, followed by analysis of data. Results- Based on the in silico approaches, we found the best interactions between ginger compounds (6-Gingerol and 6-Shogaol) and targeted protein molecules as shown less than 3.10 A0H-bond distance to indicate higher binding affinity and stronger interactions and high docking scores. We demonstrate docking interactions of 6-Gingerol with the proteins involved in angiogenesis like VEGF-A (3QTK), VEGFR-1 (5ABD), VEGFR-2/VEGF-E COMPLEX (3V6B, Angiopoietin-2 (4JZC), PDGF-B (4QCI), KDR (5EW3) and with the proteins involved in lymphangiogenesis such as VEGF-C(2XIX), VEGF-C in complex with domains of 2 and 3 of VEGFR2 (2X1W), NRP2(4QDS) and Neuropilin-1/VEGF-A complex (4DEQ). Similarly, our data shows that 6-Shogaol also interacts with angiogenic specific proteins, like [VEGF-A (3QTK), VEGFR-1 (5ABD), VEGFR-2/VEGF-E COMPLEX (3V6B), Angiopoietin-2 (4JZC), PDGF-B (4QCI), KDR (5EW3)] and lymphangiogenesis [VEGF-C(2XIX), VEGF-C in complex with domains of 2 and 3 of VEGFR2 (2X1W), NRP2(4QDS) and Neuropilin-1/VEGF-A complex (4DEQ)]. Discussion- In silico approaches suggest a stronger binding affinity between the ginger compounds (6-Gingerol and 6-Shogaol) and selected proteins critical in angiogenesis and lymphangiogenesis. The present study underlines the feasibility of neutraceuticals to target the pathways participating in breast cancer progression through neovascularization. Our results also advocate 6-Gingerol to be more potent inhibitor of lymphangiogenesis assessed by its binding efficacy with VEGF-C and NRP2 (4QDS) as compared against 6-Shogaol.\",\"PeriodicalId\":13866,\"journal\":{\"name\":\"International Journal of Chemistry\",\"volume\":\"242 1\",\"pages\":\"61-68\"},\"PeriodicalIF\":0.0000,\"publicationDate\":\"2019-12-02\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"1\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"International Journal of Chemistry\",\"FirstCategoryId\":\"1085\",\"ListUrlMain\":\"https://doi.org/10.5539/ijc.v12n1p61\",\"RegionNum\":0,\"RegionCategory\":null,\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"\",\"JCRName\":\"\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"International Journal of Chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.5539/ijc.v12n1p61","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 1

摘要

背景- 6-Gingerol和6-Shogaol是从生姜根茎中分离得到的具有生物活性的新型酚类化合物,具有抗炎、抗氧化和细胞凋亡的潜在作用。迄今为止,生姜对血管生成、淋巴管生成和转移的分子机制的功能特性尚无科学报道。因此,在本研究中,我们探索了活性姜化合物(6-Gingerol和6-Shogaol)的可行性,通过芯片方法验证其在乳腺癌进展中血管生成和淋巴管生成的分子机制。方法:通过使用Accelrys discovery studio 2.5,研究目标是发现在血管生成和淋巴管生成中起关键作用的选定蛋白质受体与姜化合物(6-Gingerol和6-Shogaol)配体之间的相互作用,然后对数据进行分析。结果-基于计算机方法,我们发现生姜化合物(6-Gingerol和6-Shogaol)与目标蛋白分子的最佳相互作用表现为小于3.10 a0h键距离,表明具有较高的结合亲和力和更强的相互作用和高对接分数。我们证实了6-姜酚与参与血管生成的蛋白如VEGF-A (3QTK)、VEGFR-1 (5ABD)、VEGFR-2/VEGF-E COMPLEX (3V6B)、血管生成素-2 (4JZC)、PDGF-B (4QCI)、KDR (5EW3)以及参与淋巴管生成的蛋白如VEGF-C(2XIX)、VEGF-C与VEGFR2 (2X1W)、NRP2(4QDS)和Neuropilin-1/VEGF-A COMPLEX (4DEQ)的2和3结构域复合物的对接相互作用。同样,我们的数据显示,6-Shogaol还与血管生成特异性蛋白相互作用,如[VEGF-A (3QTK), VEGFR-1 (5ABD), VEGFR-2/VEGF-E COMPLEX (3V6B),血管生成素-2 (4JZC), PDGF-B (4QCI), KDR (5EW3)]和淋巴管生成[VEGF-C(2XIX), VEGF-C与VEGFR2 (2X1W), NRP2(4QDS)和Neuropilin-1/VEGF-A复合物(4DEQ)的2和3结构域的复合物]。讨论-计算机方法表明生姜化合物(6-Gingerol和6-Shogaol)与血管生成和淋巴管生成中关键的特定蛋白质之间具有更强的结合亲和力。目前的研究强调了中性药物通过新血管形成参与乳腺癌进展的途径的可行性。我们的研究结果还表明,与6-Shogaol相比,6-姜辣素与VEGF-C和NRP2 (4QDS)的结合效果更强,是更有效的淋巴管生成抑制剂。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Molecular Docking Studies to Understand the Potential Role of Ginger Compounds (6-Gingerol and 6-Shogaol) on Anti-Angiogenic and Anti-Lymphangiogenic Mechanisms
Background- 6-Gingerol and 6-Shogaol are novel biologically active phenol compounds isolated from rhizomes of Ginger (Zingiber officinale Roscoe), which has a potential role as anti-inflammatory, anti-oxidant and apoptotic. Till date there are no scientific reports on the functional properties of Ginger against the molecular mechanisms of angiogenesis, lymphangiogenesis, and metastasis. Hence, in the present study we have explored the feasibility of active ginger compounds (6-Gingerol and 6-Shogaol) to validate their molecular mechanisms on angiogenesis and lymphangiogenesis in breast cancer progression through in silico approach. Methodology- Studies have been targeted to find the interactions between selected protein receptors, which play a pivotal role in angiogenesis and lymphangiogenesis and ligands of Ginger compounds (6-Gingerol and 6-Shogaol) by using Accelrys discovery studio 2.5, followed by analysis of data. Results- Based on the in silico approaches, we found the best interactions between ginger compounds (6-Gingerol and 6-Shogaol) and targeted protein molecules as shown less than 3.10 A0H-bond distance to indicate higher binding affinity and stronger interactions and high docking scores. We demonstrate docking interactions of 6-Gingerol with the proteins involved in angiogenesis like VEGF-A (3QTK), VEGFR-1 (5ABD), VEGFR-2/VEGF-E COMPLEX (3V6B, Angiopoietin-2 (4JZC), PDGF-B (4QCI), KDR (5EW3) and with the proteins involved in lymphangiogenesis such as VEGF-C(2XIX), VEGF-C in complex with domains of 2 and 3 of VEGFR2 (2X1W), NRP2(4QDS) and Neuropilin-1/VEGF-A complex (4DEQ). Similarly, our data shows that 6-Shogaol also interacts with angiogenic specific proteins, like [VEGF-A (3QTK), VEGFR-1 (5ABD), VEGFR-2/VEGF-E COMPLEX (3V6B), Angiopoietin-2 (4JZC), PDGF-B (4QCI), KDR (5EW3)] and lymphangiogenesis [VEGF-C(2XIX), VEGF-C in complex with domains of 2 and 3 of VEGFR2 (2X1W), NRP2(4QDS) and Neuropilin-1/VEGF-A complex (4DEQ)]. Discussion- In silico approaches suggest a stronger binding affinity between the ginger compounds (6-Gingerol and 6-Shogaol) and selected proteins critical in angiogenesis and lymphangiogenesis. The present study underlines the feasibility of neutraceuticals to target the pathways participating in breast cancer progression through neovascularization. Our results also advocate 6-Gingerol to be more potent inhibitor of lymphangiogenesis assessed by its binding efficacy with VEGF-C and NRP2 (4QDS) as compared against 6-Shogaol.
求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
自引率
0.00%
发文量
0
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信